Study to Evaluate the Safety and Efficacy of Telavancin in the Treatment of Gram Positive Bloodstream Infections in Cancer Patients

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01321879
• Collaborator: Theravance Biopharma (Industry)
• Enrollment: 40
• Location: 1
• Arm: 1
• Duration (Months): 69.1
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The goal of this clinical research study is to learn if Vibativ (telavancin) can help to control blood stream infections (BSIs). The safety of this treatment will also be studied.

Objectives:

Evaluate the clinical efficacy and safety of Telavancin given for treatment of gram positive bacteremia in cancer patients (including neutropenics).

Condition or Disease	Intervention/Treatment	Phase
Infection; Bacteremia	Drug: Telavancin	Phase 2

Detailed Description

The Study Drug:

Telavancin is an antibiotic designed to treat a variety of bacterial infections that are difficult to treat.

Central Venous Catheter (CVC):

A CVC is a sterile flexible tube could have been placed into a large vein while you were under local anesthesia.

If you have a certain type of infection, your doctor may decided to remove or exchange your CVC. The decision to remove or exchange the CVC and timing of the placement of the new CVC will be decided by your primary doctor.

If you are to get a new CVC, your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form.

Study Treatment:

If you are found to be eligible to take part in this study, you will receive telavancin by vein over a period of 60 minutes once daily for at least 7 days and for up to 6 weeks. How long you receive the study drug will depend on the type of bacterial infection that you have and if your doctor thinks you may have a complicated bacterial infection of the blood.

If the doctor thinks that you have a mixed infection (2 or more certain types of bacteria), you may also be given another type of antibiotic (such as aztreonam, cefepime, imipenem, meropenem, ciprofloxacin hydrochloride, bactrim, piperacillin/tazobactam and/or amoxicillin/clavulanate).

If the doctor thinks it is needed, you will have an echocardiogram to check your heart function. This test will only be performed if you have a specific type of infection (to make sure you do not have inflammation in the lining of the heart). You will be asked about medications you are taking.

If you are discharged from the hospital before completing the study drug, you will be able to take the drug as an outpatient. Your primary doctor may arrange for you to receive medication at M. D. Anderson.

Study Visits:

Once a week:

• Blood (about 1 tablespoon) will be drawn for routine tests. It may be drawn from the CVC, if the CVC is still in place.

• The CVC exit site will be checked at each visit until you have no more signs or symptoms of infection.

• You will be asked about any symptoms or illnesses that you may have had since your last visit.

Every other day, blood (about 1 tablespoon) will be drawn to check for the infection until it no longer shows signs of infection. Kidney function will be monitored by performing a blood test every 2 days for the first week and weekly after that.

Length of Study:

You can receive the study drug for up to 6 weeks. You will be taken off this study if the infection gets worse or any intolerable side effects occur.

End-of-Study Visit and Follow-up Visit:

You will need to return to MD Anderson for your end of treatment visit, within 7 days after you last dose of study drug. The end-of-study visit will occur within 7 days after your last dose of the study drug.

The follow-up visit will occur about 32 days (about 1 month) after your last dose of the study drug. At each of these visits, you will have the following exams/procedures performed.

• You will have a physical exam, including measurement of your vital signs.

• Blood (about 1 tablespoon) will be drawn for routine tests and to check for bacterial infection. The blood sample may be drawn from the CVC, if the CVC is still in place. The CVC exit site will be examined.

• You will be asked about any symptoms or illnesses that you may have had since your last visit.

• You will be asked about any drugs or therapies that you may be taking until the end of your treatment.

• If your infection recurs during the follow-up period, and if the doctor thinks it is needed, you will have an echocardiogram to check your heart function and to make sure you do not have inflammation in the lining of the heart.

This is an investigational study. Telavancin is FDA approved and commercially available for the treatment infections of the skin and soft tissue. Its use to treat blood infections in this study is investigational.

Up to 40 patients will take part in this study. All will be enrolled at M. D. Anderson.

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II, Open-Label Pilot Study to Evaluate the Safety and Efficacy of Telavancin in the Treatment of Gram Positive Bloodstream Infections in Cancer Patients
• Study Start Date: Mar 1, 2011
• Actual Primary Completion Date: Dec 1, 2016
• Actual Study Completion Date: Dec 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Telavancin 10 or 7.5 mg/kg intravenous daily	Drug: Telavancin; 10 mg/kg by vein once daily for patients with a creatinine clearance of more than 50 ml/min, and a dose of 7.5 mg/kg once daily for patients with a creatinine clearance of 30-50 ml/min.; Other Names: Vibativ

Outcome Measures

Primary Outcome Measures

1. Patient Clinical Response to Telavancin [From baseline up to 6 weeks, assessed every 7 days]

   Clinical response assessed: Cure (No fever/chills or symptoms + eradication causing organism); Improvement (Resolution local/systemic symptoms + no new systemic antibacterial treatment); Failure (IF one or more following: Persistence 1+ symptoms [fever/chills] + new systemic anti gram positive treatment, > 72 hours after initiation study drug; or Relapse within 1 month completing antibiotic therapy; or Development of deep-seated infection not previously assessed); Indeterminate (clinical signs and symptoms cannot be assessed).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients with probable or definite diagnosis of uncomplicated gram positive bacteremia that have at least one positive blood culture including 20 patients with Staphylococcus aureus and the other 20 patients will include any of the following organism ( CNS, Enterococci, streptococci, pneumococci, Corynebacterium, and Propionibacterium or Bacillus species).If the positive blood culture involves a commensal skin organism such as CNS, Corynebacterium, Propionibacterium, Micrococcus and Bacillus, then at least > 100 colonies/ml will be required or a time to positivity =/< 16 hours (as it has been shown to reflect a high grade bacteremia), or two positive blood cultures. (Time to positivity of a blood culture bottle is recorded in the microbiology laboratory by the automatic culture detector (Bactec 9240 and Bactec Plus Aerobic/F; Becton Dickinson) which records culture positivity every 15 min according to changes in fluorescence related to microbial growth).

2. Patients must have at least two signs of sepsis from the list below, in any combination at any time, within 48 hours prior to Telavancin therapy: a. Core temperature =/>38.0 degrees C or =/<36.0 degrees C, measured orally, rectally, tympanic ally or via a central catheter. If auxiliary add 0.5 degrees C to the measured temperature; b. Pulse rate =/> 100 beats/min.; c. Respiratory rate =/> 20/min.; d. WBC count =/>12,000/mm^3, =/<4,000/mm or differential count showing >10% band forms; e. Systolic blood pressure =/<90 mm Hg. Patient will still be eligible for the study if the participants white blood cell count (WBC) is outside normal limits due to chemotherapy treatment or underlying conditions.

3. Male or non-pregnant, non-lactating females with an age of greater than or equal to 18 years.

4. Signed informed consent.

5. Female patients must be at no risk for pregnancy for one of the following reasons: - Postmenopausal for at least one year - Post-hysterectomy and/or post-bilateral ovariectomy - If of childbearing potential, having a negative serum human chorionic gonadotropin (hCG) pregnancy test with in 5 days prior to enrollment and be using a highly effective method of birth control throughout the course of the study. Reliable sexual abstinence throughout the course of the study is acceptable as a highly effective method of birth control for the purposes of this study.

Exclusion Criteria:

1. Estimated Serum Creatinine Clearance <30 mL/min (according to Cock-Gault-formula using ideal body weight) at the time gram positive bacteremia was diagnosed unless the patient is on dialysis.

2. Bilirubin >4x the upper limit of normal at the time gram positive bacteremia was diagnosed.

3. Treatment with an antibiotic, such as vancomycin, linezolid, tigecycline or Telavancin, effective against resistant gram positive bacterial infections, such as methicillin resistant staphylococci, for more than 48 hours within 72 hours of study medication initiation, unless treatment failed that is defined as a persistent fever and/or leukocytosis for 72 hours or longer of appropriate antibiotics treatment.

4. History of hypersensitivity to lipoglycopeptides.

5. Presence of deep-sited intravascular source of infection with same organism cultured from blood, e.g. endocarditis (as evidenced by vegetations on an echocardiogram), or septic thrombosis.

6. Presence of a prosthetic valve.

7. Oliguria defined as urine output of <20 cc/hour averaged over 24 hours.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• Theravance Biopharma

Investigators

• Principal Investigator: Issam Raad, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• University of Texas MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT01321879
• Other Study ID Numbers: 2010-0454; NCI-2011-00752
• First Posted: Mar 24, 2011
• Last Update Posted: Dec 27, 2019
• Last Verified: Dec 1, 2019

• Keywords provided by M.D. Anderson Cancer Center: Gram Positive Bloodstream Infections; Sepsis; Staphylococcus aureus; Enterococci; Streptococci; Pneumococci; Corynebacterium; Propionibacterium or Bacillus species; Telavancin; Vibativ
• Additional relevant MeSH terms: Infections; Communicable Diseases; Bacteremia; Sepsis; Telavancin

Study Results

Participant Flow

Recruitment Details	Recruitment Period: March 2011 and May 2013. All recruitment done at The University of Texas (UT) MD Anderson Cancer Center.
Pre-assignment Detail	One participant was excluded from the study because of a failed screening test result and did not receive treatment.

Arm/Group Title	Telavancin
Arm/Group Description	Telavancin 10 mg/kg intravenous (IV) once daily for patients with a creatinine clearance of more than 50 ml/min, and a dose of 7.5 mg/kg once daily for patients with a creatinine clearance of 30-50 ml/min.
Period Title: Overall Study
STARTED	39
COMPLETED	25
NOT COMPLETED	14

Baseline Characteristics

Arm/Group Title	Telavancin
Arm/Group Description	Telavancin 10 mg/kg intravenous (IV) once daily for patients with a creatinine clearance of more than 50 ml/min, and a dose of 7.5 mg/kg once daily for patients with a creatinine clearance of 30-50 ml/min.
Overall Participants	39
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	61
Sex: Female, Male (Count of Participants)
Female	18 46.2%
Male	21 53.8%
Region of Enrollment (participants) [Number]
United States	39 100%

Outcome Measures

1. Primary Outcome

Title	Patient Clinical Response to Telavancin
Description	Clinical response assessed: Cure (No fever/chills or symptoms + eradication causing organism); Improvement (Resolution local/systemic symptoms + no new systemic antibacterial treatment); Failure (IF one or more following: Persistence 1+ symptoms [fever/chills] + new systemic anti gram positive treatment, > 72 hours after initiation study drug; or Relapse within 1 month completing antibiotic therapy; or Development of deep-seated infection not previously assessed); Indeterminate (clinical signs and symptoms cannot be assessed).
Time Frame	From baseline up to 6 weeks, assessed every 7 days

Outcome Measure Data

Analysis Population Description

Three patients received <72 hours of Telavancin treatment and therefore were excluded from the efficacy analysis.

Arm/Group Title	Telavancin
Arm/Group Description	Telavancin 10 mg/kg intravenous (IV) once daily for patients with a creatinine clearance of more than 50 ml/min, and a dose of 7.5 mg/kg once daily for patients with a creatinine clearance of 30-50 ml/min.
Measure Participants	36
Count of Participants [Participants]	32 82.1%

Adverse Events

Time Frame	Adverse event collected over duration of study drug therapy at least 7 days and up to 6 weeks.
Arm/Group Title	Telavancin
Arm/Group Description	Telavancin 10 mg/kg intravenous (IV) once daily for patients with a creatinine clearance of more than 50 ml/min, and a dose of 7.5 mg/kg once daily for patients with a creatinine clearance of 30-50 ml/min.
All Cause Mortality
	Telavancin
	Affected / at Risk (%)	# Events
Total	7/39 (17.9%)
Serious Adverse Events
	Telavancin
	Affected / at Risk (%)	# Events
Total	15/39 (38.5%)
Blood and lymphatic system disorders
Neutropenic fever	3/39 (7.7%)
Anemia	1/39 (2.6%)
Tumor lysis syndrome	1/39 (2.6%)
Cardiac disorders
Hypotension	1/39 (2.6%)
Acute coronary syndrome	1/39 (2.6%)
Gastrointestinal disorders
Intraabdominal hemorrhage	1/39 (2.6%)
Abdominal pain	1/39 (2.6%)
Bowel obstruction	1/39 (2.6%)
Hepatobiliary disorders
Hepatic failure	2/39 (5.1%)
Infections and infestations
Fever	1/39 (2.6%)
Pneumonia	1/39 (2.6%)
Bloodstream infection	1/39 (2.6%)
Sepsis	2/39 (5.1%)
Metabolism and nutrition disorders
Hypocalcemia	1/39 (2.6%)
Hypercalcemia	1/39 (2.6%)
Hyperkalemia	1/39 (2.6%)
Nervous system disorders
Intracerebellar bleed	1/39 (2.6%)
Neuropathy	1/39 (2.6%)
Renal and urinary disorders
Acute Renal Injury	2/39 (5.1%)
Respiratory, thoracic and mediastinal disorders
Respiratory Failure	4/39 (10.3%)
Dyspnea	2/39 (5.1%)
Pleural effusion	1/39 (2.6%)
Hypoxia	1/39 (2.6%)
Other (Not Including Serious) Adverse Events
	Telavancin
	Affected / at Risk (%)	# Events
Total	31/39 (79.5%)
Blood and lymphatic system disorders
Anemia	10/39 (25.6%)	13
Blood and lymphatic system disorders - (Other)	2/39 (5.1%)	2
Bruising	1/39 (2.6%)	1
Febrile neutropenia	5/39 (12.8%)	5
Cardiac disorders
Acute coronary syndrome	1/39 (2.6%)	1
Sinus tachycardia	2/39 (5.1%)	2
Eye disorders
Eye disorders - (Other)	2/39 (5.1%)	2
Floaters	1/39 (2.6%)	1
Gastrointestinal disorders
Anorexia	2/39 (5.1%)	2
Constipation	1/39 (2.6%)	1
Diarrhea	5/39 (12.8%)	5
Dysphagia	1/39 (2.6%)	1
Esophageal pain	1/39 (2.6%)	1
Gastrointestinal disorders	3/39 (7.7%)	4
Hemorrhoidal hemorrhage	1/39 (2.6%)	1
Mucositis oral	1/39 (2.6%)	2
Nausea	5/39 (12.8%)	5
General disorders
Abdominal pain	2/39 (5.1%)	2
Fatigue	2/39 (5.1%)	2
Hepatobiliary disorders
Hepatic failure	1/39 (2.6%)	1
Hepatic hemorrhage	1/39 (2.6%)	1
Infections and infestations
Hepatitis viral	1/39 (2.6%)	1
Infections and infestations - (Other)	2/39 (5.1%)	2
Pelvic infection	1/39 (2.6%)	1
Scrotal infection	1/39 (2.6%)	1
Sepsis	1/39 (2.6%)	1
Sinusitis	1/39 (2.6%)	1
Soft tissue infection	1/39 (2.6%)	1
Wound infection	1/39 (2.6%)	1
Injury, poisoning and procedural complications
Fall	1/39 (2.6%)	1
Investigations
Blood bilirubin increased	2/39 (5.1%)	2
Creatinine increased	8/39 (20.5%)	10
Fever	5/39 (12.8%)	7
Neutrophil count decreased	6/39 (15.4%)	9
Platelet count decreased	9/39 (23.1%)	15
White blood cell decreased	8/39 (20.5%)	11
Metabolism and nutrition disorders
Alanine aminotransferase increased	1/39 (2.6%)	1
Alkaline phosphatase increased	1/39 (2.6%)	1
Aspartate aminotransferase increased	1/39 (2.6%)	1
Hypercalcemia	1/39 (2.6%)	1
Hyperglycemia	3/39 (7.7%)	3
Hyperkalemia	1/39 (2.6%)	1
Hypermagnesemia	1/39 (2.6%)	1
Hyperuricemia	1/39 (2.6%)	3
Hypoalbuminemia	3/39 (7.7%)	3
Hypocalcemia	3/39 (7.7%)	3
Hypokalemia	7/39 (17.9%)	8
Hypomagnesemia	3/39 (7.7%)	4
Hyponatremia	1/39 (2.6%)	1
Hypophosphatemia	4/39 (10.3%)	5
Musculoskeletal and connective tissue disorders
Edema limbs	1/39 (2.6%)	1
Nervous system disorders
Confusion	3/39 (7.7%)	3
Intracranial hemorrhage	1/39 (2.6%)	2
Psychiatric disorders
Psychiatric disorders - (Other)	1/39 (2.6%)	1
Renal and urinary disorders
Acute kidney injury	2/39 (5.1%)	2
Hematuria	1/39 (2.6%)	1
Reproductive system and breast disorders
Menorrhagia	1/39 (2.6%)	1
Vaginal hemorrhage	1/39 (2.6%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/39 (2.6%)	1
Dyspnea	5/39 (12.8%)	5
Epistaxis	1/39 (2.6%)	1
Pleural effusion	1/39 (2.6%)	1
Pneumonitis	1/39 (2.6%)	1
Respiratory failure	1/39 (2.6%)	1
Sore throat	1/39 (2.6%)	1
Skin and subcutaneous tissue disorders
Edema face	1/39 (2.6%)	1
Skin and subcutaneous tissue disorders - (Other)	1/39 (2.6%)	1
Skin infection	1/39 (2.6%)	1
Urticaria	1/39 (2.6%)	1
Surgical and medical procedures
Surgical and medical procedures - (Other)	2/39 (5.1%)	2
Vascular disorders
Hematoma	1/39 (2.6%)	1
Hypotension	1/39 (2.6%)	1
Vascular access complication	1/39 (2.6%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.